Stability Challenges of Amorphous Solid Dispersions of Drugs: A Critical Review on Mechanistic Aspects

The most common drawback of the existing and novel drug molecules is their low bioavailability because of their low solubility. One of the most important approaches to enhance the bioavailability in the enteral route for poorly hydrophilic molecules is amorphous solid dispersion (ASD). The solubility of compounds in amorphous form is comparatively high because of the availability of free energy produced during formulation. This free energy results in the change of crystalline nature of the prepared ASD to the stable crystalline form leading to the reduced solubility of the product. Due to the intrinsic chemical and physical uncertainty and the restricted knowledge about the interactions of active molecules with the carriers making, this ASD is a challenging task. This review focused on strategies to stabilize ASD by considering the various theories explaining the free-energy concept, physical interactions, and thermal properties. This review also highlighted molecular modeling and machine learning computational advancement to stabilize ASD.